Therapeutics: K-Ras (KRAS); calmodulin; protein kinase C (PKC)

Mouse studies suggest inhibiting the KRAS-calmodulin interaction by activating PKC could help treat KRAS-driven pancreatic cancer. In a human pancreatic cell line harboring oncogenic KRAS, the PKC activator prostratin inhibited the KRAS-calmodulin interaction and decreased tumorigenic KRAS signaling and cell viability compared with vehicle. In an orthotopic xenograft mouse model of KRAS-driven pancreatic cancer, prostratin decreased tumor growth and metastasis to the peritoneum compared with vehicle. Next steps could include testing other PKC activators in models of pancreatic cancer.

Aphios Corp. has the PKC activator APH-0703 in Phase II/III testing to treat Alzheimer's disease...